Background & aims: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. Methods: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. Results: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). Conclusions: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. Clinicaltrials: gov number: NCT03107793.

Kucharzik, T., Wilkens, R., D'Agostino, M. A., Maconi, G., Le Bars, M., Lahaye, M., Bravatà, I., Nazar, M., Ni, L., Ercole, E., Allocca, M., Machková, N., De Voogd, F. A. E., Palmela, C., Vaughan, R., Maaser, C., Grega, T., Niangova, I., Repak, R., Matejkova, P., Vanickova, R., Agerbæk, J. M., Cannon, A., Mussati, G. V., Antoni, C., Büning, J., Gebel, M., Grewe, M., Küpper, S., Ryschka, N., Potthoff, A., Reindl, W., Schliwa, K., Schulz, M., Schulze, H., Krankenhaus, M., Affronti, M., De Simone, M. L., Bezzio, C., Cavallaro, F., Coletta, M., Costantino, A., Furfaro, F., Pizzolante, F., Bots, S., De Knegt, R., Bunganic, I., Opravil, Z., Poza, J., Rimola, J., Ferrer, C. S., Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease, <<CLINICAL GASTROENTEROLOGY AND HEPATOLOGY>>, 2022; 2022 (July): N/A-N/A. [doi:10.1016/j.cgh.2022.05.055] [https://hdl.handle.net/10807/221892]

Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease

D'Agostino, Maria Antonietta;Mussati, Giuliano Vittorio;De Simone, Maria Laura;Pizzolante, Fabrizio;
2022

Abstract

Background & aims: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. Methods: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. Results: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). Conclusions: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. Clinicaltrials: gov number: NCT03107793.
Inglese
Kucharzik, T., Wilkens, R., D'Agostino, M. A., Maconi, G., Le Bars, M., Lahaye, M., Bravatà, I., Nazar, M., Ni, L., Ercole, E., Allocca, M., Machková, N., De Voogd, F. A. E., Palmela, C., Vaughan, R., Maaser, C., Grega, T., Niangova, I., Repak, R., Matejkova, P., Vanickova, R., Agerbæk, J. M., Cannon, A., Mussati, G. V., Antoni, C., Büning, J., Gebel, M., Grewe, M., Küpper, S., Ryschka, N., Potthoff, A., Reindl, W., Schliwa, K., Schulz, M., Schulze, H., Krankenhaus, M., Affronti, M., De Simone, M. L., Bezzio, C., Cavallaro, F., Coletta, M., Costantino, A., Furfaro, F., Pizzolante, F., Bots, S., De Knegt, R., Bunganic, I., Opravil, Z., Poza, J., Rimola, J., Ferrer, C. S., Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease, <<CLINICAL GASTROENTEROLOGY AND HEPATOLOGY>>, 2022; 2022 (July): N/A-N/A. [doi:10.1016/j.cgh.2022.05.055] [https://hdl.handle.net/10807/221892]
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